Prenatal Blood Typing With Next Generation Sequencing (NGS) - an Implementation Study in HDFN (PREFAB)

NCT07715214 | Not Yet Recruiting

• 3 other identifiers: 2026-02336-01FoUI-1044874K 2026-6426
• Study Type: interventional
• Target: 750
• Locations: 0 countries
• Sites: N/A

Brief Summary

Determination of Fetal Blood Group by Next-Generation Sequencing - A Clinical Study in Pregnancies with Maternal Alloantibodies Directed Against Fetal Blood Cells (Alloimmunization During Pregnancy) Maternal antibodies can cross the placenta and reach the fetus during pregnancy. In some cases, these antibodies are harmful to the fetus. One such condition is alloimmunization against fetal red blood cells or platelets. This occurs in approximately 1% of all pregnancies and, if left undetected, unmonitored, and untreated, may lead to fetal anemia, heart failure, bleeding, or fetal death. Today, pregnant women are offered screening for antibodies against red blood cells during pregnancy. It is the fetus that may be affected, making the fetus the patient whose risk of disease and complications after birth healthcare aims to identify and minimize. This presents a particular challenge because, until birth, the fetus remains physically connected to and dependent on the pregnant woman. Methods are available to estimate the fetal blood group and thereby assess the risk to the unborn child. Since the fetus inherits its blood group from both biological parents, some fetuses will carry blood group antigens that are targeted by the mother's antibodies, while others will not. Current methods are imperfect, and in approximately 30% of cases the fetus will not carry the relevant blood group antigen. Consequently, many pregnancies undergo unnecessary monitoring, causing additional healthcare costs as well as anxiety for the pregnant woman and her partner. Using advanced genetic technology, we aim to investigate whether analysis of a maternal blood sample by Next-Generation Sequencing (NGS) can accurately determine the fetal blood group. This would enable reliable identification of fetuses at risk of being affected by maternal alloantibodies, while also identifying those that are not at risk and therefore do not require unnecessary monitoring. NGS will be used in a study population in Sweden (seven centers) and validated for patient safety, logistic implementation and health economic costs.

Conditions

Red Blood Cell Alloimmunization in Pregnancy; HDFN; Next Generation Sequencing (NGS)

Keywords

Fetal red blood cell antigen; next generation sequencing of cell free fetal DNA

Outcome Measures

Primary Outcomes (1)

• Implementation patient safety composite

  Patient safety assessment defined as a composite outcome including: 1. Gestational age (days) at blood sampling for fetal antigen test 2. Number of second confirming samples (n) 3. Turn around time for NGS analyses and report to clinicians (days) 4. Numbers and percentage of fetuses negative for the maternal antibody corresponding antigen according to NGS analysis (n, %) 5. Concordance of fetal antigen according to NGS compared to neonatal cord blood analysis (%)

  From the date of inclusion until birth

Other Outcomes (1)

• Obstetric and neonatal outcomes.

  From inclusion until 28 days after birth

Study Arms (1)

NGS for cell free fetal DNA in red blod cell alloimmunization in pregnancy

OTHER

NGS analyses of cell free fetal DNA in maternal plasma

Diagnostic Test: NGS analysis for fetal red cell blood type in maternal plasma

Interventions

NGS analysis for fetal red cell blood type in maternal plasma DIAGNOSTIC_TEST

NGS of cell free fetal DNA in maternal plasma for all prospective identified red cell alloimmunization in early pregnancy within seven regions in Sweden. None included regions in Sweden will be analyses according to ongoing clinical routine, that is paternal phenotype identification or follow the pregnancy by repeated maternal antibody titers.

NGS for cell free fetal DNA in red blod cell alloimmunization in pregnancy

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- red blood cell alloimmunized pregnancies in the participating regions during the study period

You may not qualify if:

• Miscarriage and terminations of pregnancy for other reasons than severe alloimmunization

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Karolinska Institutet: collaborator
• University Hospital, Umeå: collaborator
• Uppsala University Hospital: collaborator
• Sahlgrenska University Hospital: collaborator
• Skane University Hospital: collaborator
• University Hospital, Linkoeping: collaborator
• Dept of Obstet & Gynecol, University Hospital Oerebro: collaborator

Related Publications (1)

• Emahazion T, Badri A, Jalkesten E, Flodstrom M, Ajne G, Uzunel M, Wikman A. Next-generation sequencing-based approach for fetal DNA quantification and blood antigen detection in alloimmunized pregnancies. Am J Obstet Gynecol MFM. 2025 Jul;7(7):101694. doi: 10.1016/j.ajogmf.2025.101694. Epub 2025 May 13.

  PMID: 40373875 RESULT

Related Links

• Swedish website for red blood cell immunization in pregnancy

Study Officials

• Gunilla Ajne, PhD, MD

  Karolinska Institutet, Clintec, Div of Obstet&Gyne AND Karolinska University Hospital Stockholm Sweden

  PRINCIPAL INVESTIGATOR

• Agneta Wikman, Adj prof, MD

  Karolinska Institutet, Centre Hematol & Regen Med AND Clin Immunology & Transf Med Karolinska University Hospital

  STUDY CHAIR

• Tesfai Emahazion, PhD

  Karolinska Institutet, Centre Hematol & Regen Med AND Clin Immunology & Transf Med Karolinska University Hospital

  STUDY DIRECTOR

Central Study Contacts

Gunilla Ajne, PhD, MD

CONTACT

+46 812386953; gunilla.ajne@regionstockholm.se

Johanna S Andersson, MD, PhD stud

CONTACT

+46 812380000; johanna.so.andersson@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, associated professor, MD, senior consultant in Obstetrics & Gynecology

Model Details: Implemenation of NGS for cell free fetal DNA in maternal plasma in red cell alloimmunized pregnancy in seven university regions in Sweden

Study Record Dates

• First Submitted: July 10, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share